Long-term in vivo behavior and corneal endothelial toxicity of intracameral tobramycin-dexamethasone ointment in rats

The inadvertent entry of ophthalmic ointment into the anterior chamber following intraocular surgery can cause vision-threatening complications. However, the exact in vivo behavior and cytotoxic mechanisms remain poorly understood. This experimental study aimed to investigate the dynamic morphological evolution and underlying molecular mechanisms of corneal endothelial toxicity caused by retained intracameral tobramycin-dexamethasone ointment. A Sprague-Dawley rat model of anterior chamber ointment retention was established by micro-injecting tobramycin-dexamethasone ointment into the anterior chamber. The eyes were monitored continuously for up to 15 weeks using slit-lamp examination, anterior segment optical coherence tomography (AS-OCT), in vivo confocal microscopy (IVCM), and posterior segment OCT. Endothelial injury and functional integrity were evaluated through histopathological analysis and immunofluorescence staining for zonula occludens-1 (ZO-1) and Na + -K + -ATPase. The retained ointment exhibited two distinct morphological patterns: localized boluses (4/6, 66.7%) and diffuse emulsification (2/6, 33.3%). Throughout the 105-day observation period, the model group showed persistent endothelial pleomorphism and a significant, continuous reduction in cell density ( P < 0.05). Immunofluorescence revealed profound downregulation and structural disruption of ZO-1 and Na + -K + -ATPase, indicating simultaneous impairment of both endothelial barrier and pump functions. Furthermore, focal angle obstruction by an ointment bolus triggered severe anterior segment complications in one case, characterized by acute bullous keratopathy, Descemet’s membrane detachment, and marked inflammatory infiltration resembling toxic anterior segment syndrome (TASS). No posterior segment abnormalities were detected across all model eyes. Inadvertent intracameral ingress of tobramycin-dexamethasone ointment disrupts crucial endothelial barrier and pump functions, leading to sustained and irreversible cell toxicity. The potential risk of severe acute complications under specific conditions underscores the critical importance of ensuring watertight surgical wound closure and prompt clinical intervention for retained intraocular ointment.